Most refugees who arrive at the Mediterranean coast of Italy and other southern European countries are leaving areas where sickle cell disease (SCD) is highly prevalent, but few strategies are in place for providing health screenings for migrants. According to a retrospective study published in Blood, this lack of screening delays diagnosis and, ultimately, contributes to higher health care costs for the host country.
“Our data strongly support routine screening for SCD in refugees from countries endemic for SCD within 10 to 14 days [of] arrival to identify potentially vulnerable patients, a structured and collaborative national network, and education of emergency physicians to identify and treat acute SCD-related events,” Lucia De Franceschi, MD, study author from Azienda Ospedaliera Universitaria Integrata and the University of Verona in Italy, told ASH Clinical News. “In the meantime, we hope that our data might open international political and social discussions about the accessibility of health care for refugees to treat both acute and chronic complications related to SCD.”
In this study, researchers collected data from 13 Italian centers to determine the number of new SCD and hemoglobinopathies diagnosed among refugees who arrived between 2014 and 2017.
During this four-year period, a total of 624,688 people had migrated to Italy. “Refugees from Syria represented only 4% to 25% of these each year,” the authors wrote, “whereas 21% to 53% came from sub-Saharan African countries.” They also observed that, while refugees are screened for communicable diseases and undergo a vaccination program within two weeks of arrival, screening for SCD is not performed.
Still, SCD was relatively common in refugees: In total, the researchers identified 70 patients with hemoglobinopathies, half of whom were children, who arrived in Italy during the four-year study period. The genotypic distribution of sickle cell was as follows:
- homozygous SS genotype: 49 patients
- hemoglobin SC genotype: 9 patients
- transfusion-dependent beta thalassemia: 6 patients
- beta thalassemia: 3 patients
- hemoglobin C disease: 2 patients
- heterozygous AS genotype: 1 patient
Most patients with the sickle cell genotype were from West African countries, while patients with transfusion-dependent beta thalassemia were often from Syria (7.1%) and Bangladesh (1.4%).
Overall, most patients with SCD had a diagnosis within 11 months of their arrival (82.9%), and 14.3% were diagnosed in the second year.
Typically, an SCD diagnosis was made after the patient presented to an emergency department with an acute event, mostly for treatment of a vaso-occlusive crisis or anemia. Various factors associated with refugees’ long journeys – including dehydration, psychological distress, and exposure to high and low temperatures – can often trigger vaso-occlusive events in SCD patients, making screening a necessity, the researchers explained.
“We hope that our data might open political and social discussions discussions about the accessibility of health care for refugees to treat complications related to SCD.”
—Lucia De Franceschi, MD
In the small group of patients who received a diagnosis of SCD outside of acute events, 2.9% were identified through early pregnancy counseling or through the management of pregnancy complications related to severe clinical manifestations due to SCD (including venous cerebral thrombosis) or obstetrical complications. Less than 3% of the remaining patients received SCD screening or had direct access to a comprehensive SCD center.
“Collectively, our results indicate the need for screening for SCD in refugees at their arrival to prevent severe acute and life-threatening clinical manifestations,” the authors wrote. To expedite the identification of SCD – and mitigate complications – the researchers undertook a pilot study in which they performed point-of-care screening with an immunoassay designed to rapidly diagnoses SCD or all refugees seen in a single refugee center during October 2017.
More than 400 individuals were screened for SCD. Three percent were found to have SCD and 20% were found to have the heterozygous AS genotype. The majority of sickle hemoglobin (HbS) carriers were from West Africa, and the authors noted that “none of the newly identified SCD patients were aware of their condition.”
Limitations of the study include its retrospective nature, Dr. Franceschi explained, as well as the use of a single center for the pilot study. Despite the limitations, she believes the data strongly support early screening for SCD in refugees from SCD-endemic areas, followed by treatment with hydroxyurea and management at a comprehensive sickle cell center.
These findings also prompted the researchers to propose several initiatives to improve screening of SCD among migrants arriving to southern Europe, including:
- the development and use of flow charts that may facilitate early identification of SCD in migrants at the time of their arrival or during their stay in second-level refugee camps
- education for health professionals (such as emergency physicians, pediatricians, internal medicine doctors, and hematologists) on the importance of early identification and management of SCD-related acute vaso-occlusive events
- rapid referrals of refugees with SCD or symptomatic HbS-carrier genotype to a comprehensive SCD reference center
- earlier initiation of disease-modifying treatment (e.g., hydroxyurea)
The authors report no relevant conflicts of interest.
De Franceschi L, Lux C, Piel FB, et al. Access to emergency departments for acute events and identification of sickle cell disease in refugees. Blood. 2019;133:2100-03.
Universal newborn screening for sickle cell disease (SCD) in the U.S. identifies almost all affected children and permits early interventions to prevent life threatening complications. A similar approach has not been consistently applied to immigrants or refugees to the U.S. In their letter to Blood, De Franceschi and colleagues describe the Italian experience diagnosing new cases of SCD and other hemoglobinopathies in refugees between 2014 and 2017 at 13 Italian reference centers for hemoglobinopathies. During this period, more than 600,000 refugees arrived in Italy, mostly from Africa and the Middle East. They diagnosed 61 new patients with SCD, six with transfusion-dependent beta-thalassemia, and three with other hemoglobinopathies. A pilot screening program using a point-of-care test with confirmation by high performance liquid chromatography in 400 refugees identified 3% with SCD and another 20% with sickle cell trait.
Approximately two-thirds of the 70 patients were diagnosed after an acute complication required emergency care and some of these complications were life-threatening and likely preventable with early diagnosis and treatment. These results support the need for screening refugees from Africa and the Middle East for hemoglobinopathies. The discordance between the relatively low number of new patients identified by the hemoglobinopathy centers (approximately 1 in 9,000 refugees) and the high prevalence of SCD in the pilot study of screening (3 in 100 refugees) is surprising, but even if the prevalence is substantially lower, screening is likely to be cost effective.
Further study is required to identify the best screening strategies (point-of-care testing vs. central laboratory) and approaches to provide newly diagnosed patients with comprehensive care.
John J. Strouse, MD, PhD
Duke University School of Medicine